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Normal anatomy, absent appendix, diverticulosis, duplication, endometriosis, inverted appendix, inverted appendiceal stump, intussusception, lymphoid hyperplasia, myxoglobulosis, necrotizing arteritis
Appendicitis: acute, chronic, Crohn’s disease, Enterobius, eosinophilic, granulomatous, infectious mononucleosis, malakoplakia, measles, periappendicitis, Schistosoma, Strongyloides, ulcerative colitis, xanthogranulomatous, Yersinia
Benign tumors: adenoma (noncystic), fibrous obliteration/neuroma, granular cell tumor, hyperplastic polyp / mucinous hyperplasia, mucinous cystadenoma, mucocele, neurofibroma, simple mucocele
Carcinoma: adenocarcinoma, coexisting appendiceal and ovarian neoplasms, metastases, mucinous cystadenocarcinoma, other primaries, pseudomyxoma peritonei, signet ring cell adenocarcinoma, small cell
Endocrine tumors: general, carcinoid, L-cell carcinoid, goblet cell carcinoid
Other tumors: gastrointestinal stromal tumors, lymphoma
Staging, grossing, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), March 1977 to April 2005
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to April 2005
Human Pathology (Hum Path), March 1977 to March 2005
Modern Pathology (Mod Path), Jan 1998 to April 2005
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Sternberg: Histology for Pathologists (2nd edition), 1997
Journal search terms: appendix
Please refer to these primary references for more detailed discussions and photographs
May have role in mucosal immunity, but no definite known function
Arises from posteriomedial cecum, usually lies posterior to cecum or ascending colon, may overly pelvic brim and impinge on bladder; also other locations
Same 4 layers as gut (mucosa, submucosa, muscularis externa/propria, serosa)
Locate by following the 3 teniae coli of the large bowel, which all terminate at base of appendix
Orifice is 2.5 cm below ileocecal value; may be covered by small flap of mucosa
Vascular supply from posterior cecal branch of ileocolic artery, a branch of superior mesenteric artery
Drains into ileocolic vein, then superior mesenteric vein and portal circulation
Lymphatics drain into ileocolic lymph nodes
Innervation from vagus nerve and superior mesenteric plexus
Mesoappendix: adipose tissue plus appendiceal vessels and occasionally small lymph nodes; anchors appendix
Gross: wormlike (vermiform), mean 6-8 cm long in adults; range 2 cm (infants) to 15 cm; mean diameter 0.7 cm; distal appendix may undergo fibrous obliteration in elderly (see below); some patients have fibrous cord from birth; serosa smooth, glistening, transparent; cross section may be stellate due to lymphoid aggregates
Micro: large bowel type epithelium overlying lamina propria with irregularly distributed crypts (glands); rich lymphoid tissue in mucosa and submucosa that may disrupt the muscularis mucosa, obliterate the lumen and distort the crypt architecture (lymphoid tissue atrophies with age); epithelium contains occasional Paneth cells at crypt bases (basal nucleus, conspicuous nucleoli, abundant eosinophilic supranuclear granules); lamina propria also contains histiocytes, occasional eosinophils, neuroendocrine cells; muscularis mucosa and submucosa may be inconspicuous; muscularis propria contains complete longitudinal and circular layers and prominent ganglion cells
Associated with normal or malformed cecum
Uncommon, in 0.004% to 2% of appendectomies
More likely acquired than congenital
Usually multiple diverticuli if present; due to increased intraluminal pressure and wall weakness
Present in 14% of cystic fibrosis patients vs. 1-2% of general population (Hum Path 1987;18:75)
May cause diverticulitis, which clinically resembles appendicitis
If associated with low grade mucinous lesions, may cause pseudomyxoma peritonei (Mod Path 2000;13:495)
Gross: usually < 5 mm
Micro: herniation of mucosa and muscularis mucosa through wall of the appendix
Usually has complete and separate inner circular and outer longitudinal muscle bands, and prominent lymphoid component
Type A: common base, single cecum and bifurcated distal portion; usually incidental finding
Type B: two separate appendices with distinct bases arising from common cecum; associated with other system anomalies, but usually incidental finding
Type C: two cecal structures, each with its own single appendix; associated with other organ duplications, extensive corrective surgery required
Women of reproductive age or post-menopausal women with hormone replacement therapy
Appendix is common site of intestinal involvement
Associated with endometrial hyperplasia, MMMT, endometrial carcinoma
Case reports: mucocele of appendix secondary to obstruction by endometriosis (Hum Path 1977;8:585)
Gross: serosal nodule or blood-filled (“chocolate”) cyst; rarely causes appendiceal rupture
Micro: endometrial glands, endometrial stroma, hemosiderin; may have muscular hypertrophy, overlying mucosa may be ulcerated; no dysplasia
Positive stains: CD10 (stroma)
DD: invasive well differentiated adenocarcinoma
Appendix is inverted into cecum and appears as a polyp
Congenital or due to intussusception
Gross: cecal polyp
Micro: normal mucosa with numerous lymphoid follicles
Gross: stump resembles a polyp at appendiceal orifice in patients post-appendectomy, usually with purse-string suture
Due to invagination of entire appendix or only base into cecal lumen
Often women, mean 46 years old (range 37-70 years)
Often due to lymphoid hyperplasia, endometriosis or adenoma
May be associated with adenovirus infection or appendicitis (Archives 1990;114:106, Hum Path 1981;12:193)
Gross: inverted appendix
References: Archives 1992;116:960
Normal appendix is rich in lymphoid tissue
May be associated with acute appendicitis (? cause or effect)
Gross: may be present at entrance to cecum
Micro: marked swelling and thickening of mucosa and submucosa, with virtual luminal obliteration; older patients also have plasma cells and eosinophils
Rare cause of appendiceal dilation
Descriptive term that does not imply any specific pathologic process
Presents either as acute abdomen or as incidental finding at laparotomy or autopsy
Micro: intraluminal mucinous and pearl-like globules which may calcify; globules composed of faintly eosinophilic laminated mucin surrounding an amorphous core
References: AJSP 1988;12:962
Necrotizing arteritis of vermiform appendix
Uncommon (0.3% of examined appendixes)
Associated with systemic necrotizing arteritis in 3 of 9 cases studied
References: Archives 1988;112:738
Appendicitis
Formerly called typhilitis (inflammation of cecum)
Common in US and Great Britain (Western world); rare in Asia and Africa; associated with reduced bulk / high protein diet
Associated with obstruction in 50-80% of cases, usually due to a fecalith; also gallstone, tumor, Enterobius vermicularis (pinworms), diffuse lymphoid hyperplasia (children); however, not all cases show clear evidence of lumen obstruction
Obstruction causes increased intraluminal pressure, collapse of draining veins, ischemia, mucosal injury and ulceration, bacterial overgrowth, more edema, more ischemia
Usually teenagers or young adults who present with periumbilical to right lower quadrant pain, nausea, vomiting, abdominal tenderness, mild fever, leukocytosis (15-20,000), elevated C reactive protein, elevated sedimentation rate
May have right flank pain or pelvic pain with retrocecal appendix; pain in left upper quadrant if malrotated colon
Nonclassic presentations occur in very young or very old
Normal false positive rate for appendectomy is 20%; patients with clinical symptoms but histologically normal appendices often have neuronal hypertrophy (Archives 2003;127:573), and increased levels of inflammatory mediators (Archives 2001;125:759)
Not associated with Helicobacter pylori infection (Archives 2000;124:941)
Complications: wall abscess and perforation (2% mortality), rupture, peritonitis, pylephlebitis with thrombosis of portal venous drainage, liver abscess, bacteremia, sinus tract (often due to Actinomyces)
Diagnosis: acute inflammation (neutrophils) within appendix
Case reports: associated with Kaposi’s sarcoma of appendix (Archives 1991;115:1157)
Treatment: excision
Gross: fibrinopurulent exudate on serosa, prominent vessels; lumen may contain blood-tinged pus; may be areas of perforation, mucosal ulceration, fecalith or other obstructing agent
Micro: mucosal ulceration; minimal (if early) to dense neutrophils in muscularis propria with necrosis, congestion, perivascular neutrophilic infiltrate; late - absent mucosa, necrotic wall, prominent fibrosis, granulation tissue, marked chronic inflammatory infiltrate in wall, thrombosed vessels
DD: drainage of exudate (Campylobacter) into appendix with neutrophils in mucosa, but not wall; mesenteric lymphadenitis due to Yersinia or viral enterocolitis; systemic viral infection, acute salpingitis, ectopic pregnancy, mittelschmerz, cystic fibrosis, Meckel’s diverticulitis, acute diverticulitis, infarction of greater omentum, chemotherapy induced typhilitis
References: Hum Path 1981;12:870
Existence disputed clinically and pathologically
Some cases may represent recurrent acute appendicitis
No distinct pathologic features
Involves appendix in 25% of patients, may simulate acute appendicitis
Rare to initially or only involve the appendix
If limited to appendix, consider as granulomatous appendicitis; 90% of these patients do NOT develop disease elsewhere in GI tract
Diagnostic criteria: granulomas, transmural lymphoid aggregates, fissure-type ulcers
DD: Yersinia, Mycobacteria or Actinomyces infections
Also known as pinworm; formerly known as oxyuris vermicularis, oxyuriasis
Usually found in appendix of children ages 7-11 as incidental finding; doesn’t cause appendicitis unless mass of worms causes obstruction
Frequently invades lower female genital tract
Micro: cross section has narrow lateral cuticular alae; causes granulomas
Diffuse eosinophilic infiltrate with variable granulomas with necrotic centers
Associated with Strongyloides stercoralis in stool examinations, but usually not within the granulomas
Also associated with eosinophilic gastroenteritis
Occurs in 0.1% to 2.0% of appendectomies
Clinically resembles acute appendicitis
Histologically resembles Crohn’s disease although only 5-10% develop Crohn’s disease in GI tract
Does not recur after appendectomy
Causes: usually idiopathic, also Yersinia, pinworm (Enterobius vermicularis), sarcoidosis, foreign body reactions, Mycobacterium tuberculosis
Micro: focal cryptitis, crypt abscesses, mucosal erosion and ulceration, fissures, transmural lymphoid aggregates, mural fibrosis; usually no fistulas; more granulomas than Crohn’s (20 vs. 0.3 per tissue section)
References: Hum Path 1993;24:595, Hum Path 1986;17:1116
Associated with marked lymphoid hyperplasia in appendix accompanied by small lymphoid cells and immunoblasts resembling Reed-Sternberg cells
Usually self limited, but may cause death
References: Archives 1993;117:269, Archives 1985;109:680
Unusual in appendix (< 10 cases reported)
Commonly involves bladder; associated at all sites with tumors (lymphoma, colonic tumors), infections (TB, fungi), sarcoidosis, immunocompromise (malnutrition, diabetes, alcoholic liver disease, steroids)
Case report: mass composed of eggs of Taenia (tapeworm) species (Archives 2000;124:1828)
Micro: infiltrate of large granular eosinophilic macrophages with concentrically laminated siderocalcific Michaelis-Gutmann (MG) bodies
EM: concentric crystalline laminations with dense inner zone containing partially digested bacteria and thin outer zone
Associated with appendicitis in prodromal stage
Micro: marked lymphoid hyperplasia, multinucleated giant cells (Warthin-Finkeldey type)
Acute or chronic inflammation of serosa (beyond that seen with surgical manipulation)
Associated with advanced appendicitis and spread of inflammatory process from another site
Common, usually doesn’t cause acute appendicitis
Reference: numerous Schistosoma images
Case report of 50 year old man with Stronglyoides larva in appendix surrounded by eosinophilic granuloma (Archives 1981;105:148)
50% of cases involve appendix
Usually continuous with cecal disease
Xanthogranulomatous inflammation
Considered an unusual healing pattern of appendicitis
Micro: prominent histiocytes with clusters of xanthoma-type cells
DD: malakoplakia, Mycobacterium avium-intracellulare infection, Whipple's disease
Yersinia granulomatous appendicitis
Detected in 25% (10 of 40) cases of granulomatous appendicitis by PCR, either Y. enterocolitica or Y. pseudotuberculosis (AJSP 2001;25:508)
Some patients may develop Crohn’s disease
Histology similar to non-Yersinia granulomatous appendicitis (differentiate by PCR)
Micro: epithelioid granulomas with lymphoid cuffing, transmural inflammation with lymphoid aggregates, mucosal ulceration, cryptitis, usually no bacteria identified
Benign tumors
Very rare
Cystic adenomas are called cystadenomas (see below)
Villous adenomas are also called low grade appendiceal mucinous neoplasms
Sporadic, may be associated with colonic adenomas or familial adenomatous polyposis
By definition, no features of true invasion
Micro: resemble colonic tubular, villous or tubulovillous adenomas; cellular crowding, usually low grade dysplastic changes of nuclear elongation and stratification, pleomorphism and increased mitotic figures; also mucin depletion; no invasion into appendiceal wall or high grade nuclear atypia
Also called appendiceal neuroma
Common, in 27% of surgical specimens (AJSP 1986;10:801)
Gross: usually no gross tumor; usually affects distal tip, may affect entire lumen
Micro: lumen replaced by spindle cells in loose fibromyxoid background with chronic inflammatory cells (including eosinophils), hypertrophied nerve bundles, neuroendocrine cells, fat and collagen; loss of lymphoid follicles, mucosa and crypts; spindle cells may expand the lamina propria and separate the crypts
Intramucosal neuroma: primarily affects the mucosa, does not obliterate the lumen
Positive
stains (spindle cells):
S100, chromogranin, neuron specific enolase
EM: spindle cells resemble Schwann cells
DD: carcinoid tumor (definite insular pattern of neoplastic cells, extending into muscularis propria, associated with gross nodule or thickening of appendiceal wall)
Not a common site for this tumor
Micro: polygonal cells with granular cytoplasm and bland nuclei
Positive stains: S100, PAS
DD: granular cell transformation of appendiceal smooth muscle (negative S100)
Hyperplastic polyp / mucinous hyperplasia
Often in women, which may reflect higher incidence of incidental appendectomy in women
Usually age 40+ years
Associated with adenocarcinoma of right colon, although not precancerous per se
Gross: usually sessile or flat; may appear as diffuse lesion without well-defined borders
Micro: resembles colonic hyperplastic polyp; columnar and goblet cell proliferation with elongated and dilated tubules; luminal outlines are serrated; minimal hyperchromasia and no stratification
DD: villous adenoma (dysplastic nuclei)
Most common mucinous neoplasm of appendix
Also called low grade appendiceal mucinous neoplasm
May be associated with ovarian mucinous cystadenoma and colonic neoplasms
May present with pain due to distention, symptoms of acute appendicitis, pseudomyxoma peritonei or as abdominal mass
May represent a continuum with noncystic adenomas
Peaks in 60’s (age)
When associated with diverticula (30-40% of time), may cause pseudomyxoma peritonei (Mod Path 2000;13:495)
Sample thoroughly to rule out areas of malignancy
If spread beyond appendix, survival rates were 100%, 86% and 45% at 3-, 5- and 10- years on one study (AJSP 2003;27:1089)
Treatment: excision; low recurrence rate if low grade features and confined to appendix
Case reports: mucinous cystadenoma of pancreas and appendix (JOP. J Pancreas (Online) 2004; 5:97)
Gross: variable cystic luminal dilation, usually filled with viscid mucus; 20% perforate appendix; mucin often attached to serosa or free in peritoneal cavity
Micro: usually intestinal type epithelium (crowded columnar cells with basal, elongated, hyperchromatic nuclei, often with large amounts of apical mucin); dysplastic changes often minimal but greatest at crypt bases; high grade dysplastic changes less common; villous adenomas may completely replace appendiceal mucosa; may resemble serrated adenoma (mixed hyperplastic polyp and adenoma) or borderline ovarian mucinous tumor; occasionally see foreign body giant cell reaction, granulation tissue, chronic inflammation, fibrosis, calcification, displaced epithelium or mucin within muscularis propria; muscularis mucosa may be thin/absent and replaced with hyalinization / fibrosis; rarely heterotopic bone formation (Archives 1996;120:666)
Negative stains: CK7 (usually)
DD: retention cyst or simple mucocele (usually < 1 cm, no neoplastic epithelium despite extensive sampling), invasive adenocarcinoma (infiltrative pattern, desmoplastic stroma)
References: Hum Path 1997;28:1039, AJSP 2001;25:1095 (images)
Definition: grossly dilated appendix filled with mucus; clinical but not a histologic diagnosis
Causes: hyperplastic polyp (similar to colonic polyp), mucinous cystadenoma (most common), mucinous cystadenocarcinoma, simple mucocele (below), obstruction from endometriosis, inspissated mucus (cystic fibrosis)
Gross: nonneoplastic mucoceles usually 1 cm or less
Micro: dilatation of lumen by tenacious mucinous secretion; thin appendiceal wall; dysplastic epithelium in neoplastic lesions, mucin may dissect into wall
Rare, may be associated with von Recklinghausen’s disease or sporadic
Also called obstructed appendix with intraluminal mucin accumulation, retention cyst
Usually 5-6 mm
Micro: no neoplastic epithelium despite extensive sampling
DD: cystadenoma (neoplastic epithelium)
Carcinoma
Rare, 0.2% of appendectomy specimens
Associated with appendiceal adenoma or rupture of appendix
Usually ages 40-69 years (similar to colonic adenocarcinoma)
75% are symptomatic, with symptoms of acute appendicitis, abdominal mass or intestinal obstruction
Cases with mixed carcinoid-adenocarcinoma behave as adenocarcinoma
Mucinous cases typically present with pseudomyxoma peritonei
Treatment: appendectomy if well-differentiated and superficial, otherwise right hemicolectomy
Case reports: 35 year old woman with mixed small cell carcinoma and intestinal type adenocarcinoma (AJSP 2004;28:1233)
Gross: cystic (cystadenocarcinoma, see below) or noncystic; appendix may be buried within the mass
Micro: intestinal, mucinous or signet ring cell types, invasive ; often coexisting acute appendicitis
Positive stains: MUC2, MUC5AC (67%), CK8/18, CK13, CK19, CK20
Negative stains: MUC1 (usually), MUC6, CK7 (usually), CK14, p53
Molecular: Kras mutations in 55%, no microsatellite instability present
DD: metastatic gastric or breast carcinoma (for signet ring types)
References: Mod Path 2003;16:403, Mod Path 2002;15:599
Coexisting appendiceal and ovarian neoplasms
What were formerly called concurrent tumors are likely appendiceal metastases to ovary (AJSP 1996;20:739, AJSP 1994;18:591, AJSP 1991;15:415, Hum Path 1997;28:1039)
Ovary to appendix metastases are typically limited to outer appendiceal wall, serosa, subserosa; associated with disease at other sites
Recommendation: if pseudomyxoma peritonei and mucinous neoplasm of apparent ovarian origin (or bilateral ovarian mucinous tumors), do appendectomy (if possible, submit completely for microscopic exam) or at least inspect at operation
References: Archives 1986;110:336, Archives 1985;109:930
Usually from female breast, GI tract, female gynecologic tract
Resembles ovarian tumor, 20% as common as cystadenoma
May present with pain due to distention of the viscus
Associated with pseudomyxoma peritonei, particularly if ruptures
Gross: resembles cystadenoma
Micro: malignant cells (destructive invasion of appendiceal wall, extensive full-thickness nuclear stratification, vesicular nuclei, marked nuclear membrane abnormalities, prominent nucleoli, frequent mitotic figures, complex papillary fronds, cribriform glandular spaces) in wall with desmoplastic stromal response; some authors also classify as malignant if epithelial cells (which may appear benign) in peritoneal mucinous deposits
Molecular: 18q-
Large cecal carcinomas may involve appendix
Clinical syndrome of extravasation of mucin into abdomen outside of right lower quadrant; not a histologic diagnosis
Poor prognosis due to infection, intestinal obstruction, peritonitis
Appears to be clonally derived from associated mucinous tumor, usually of appendix (AJSP 2001;25:1095)
Also associated with ovarian mucinous tumors, although these are probably metastatic from appendix or other GI sites (AJSP 2000;24:1447, AJSP 1996;20:739, AJSP 1994;18:591, AJSP 1991;15:415)
Proposed classification systems: disseminated peritoneal adenomucinosis (associated with cystadenoma), and two types of peritoneal mucinous carcinomatosis (an aggressive type and an intermediate type, both associated with carcinoma, AJSP 1995;19:1390, AJSP 2003;27:650)
Peritoneal adenomucinosis: multifocal mucinous tumors adherent to but not invading into visceral and parietal peritoneal surfaces; peritoneal lesions contain scant histologically benign mucinous epithelium within abundant extracellular mucin; intense hyalinizing fibrotic reaction separates pools of mucin; noninvasive involvement of the parietal peritoneal surfaces with sparing of peritoneal surfaces of bowel and its mesentery
Mucinous adenocarcinoma: invasive peritoneal lesions composed of abundant epithelium with glandular or signet-ring cell morphology with malignant architectural complexity or cytological atypia; separated into well-differentiated (composed predominantly of single tubular glands; tumor cells well polarized similar to adenomatous epithelium, prominent atypia, invasive component present); moderately differentiated (characteristics between well- and poorly differentiated adenocarcinoma; composed of solid sheets of malignant cells mixed with glandular formations, minimal/absent polarity of tumor cells) and poorly differentiated (composed of highly irregular glandular structures or no glandular differentiation, no tumor cell polarity, variable signet-ring cells)
Hybrid appendiceal mucinous tumors: foci of diffuse peritoneal adenomucinosis and mucinous adenocarcinoma
Mucinous appendiceal tumors with pseudomyxoma peritonei over time and with repeated surgical and intraperitoneal chemotherapy interventions may change to a more invasive process
Poorer prognosis: presence of any epithelium within mucin (low grade or high grade, although high grade may be worse), invasive adenocarcinoma, bulky peritoneal disease
Micro: viable but bland epithelial glandular cells within large pools of mucus, also hyperemic vessels and chronic inflammatory cells
Positive stains: MUC2
DD: ruptured mucinous cystadenomas of appendix or ovary
Signet ring cell adenocarcinoma
Rare, poor prognosis
May occur with goblet cell carcinoid
Stage using TNM (below), based on depth of malignant epithelioid cells, not depth of dissecting mucus
Treatment: right hemicolectomy, remove mucus and peritoneal implants carefully; debulk if recurrent disease
Micro: resembles similar tumor elsewhere in GI tract
DD: goblet cell carcinoid (arises from glandular mucosa, spares luminal mucosa, insular pattern, no desmoplasia, better prognosis)
Very rare
Case report of 35 year old woman with mixed small cell carcinoma and intestinal type adenocarcinoma (AJSP 2004;28:1233)
Endocrine tumors
Appendix is common site for endocrine tumors, as well as tumors with multiple directional differentiation
Most common tumor of appendix, usually incidental (0.02% to 1.5% of all appendectomy specimens)
Incidence peaks at ages 20-39 years (20 years earlier than intestinal carcinoid)
20% of all GI carcinoids arise in appendix
Usually sporadic
Two types of well differentiated (carcinoid) tumors: EC cell (serotonin producing) and rarely L-cell (enteroglucagon or peptide YY producing)
Nodal metastases and metastatic spread are rare, even with transmural extension
5 year survival is 85% even with regional metastases
Rare liver metastases may be associated with carcinoid syndrome
Treatment: appendectomy usually is curative if less than 1 cm; right hemicolectomy if > 2 cm or positive surgical margin or extremely pronounced mesoappendiceal spread; perineural or angiolymphatic invasion are not predictive
Prognostic factors for metastatic disease: size of primary tumor (30% in tumors 2 cm or more); mesoappendix invasion
Case reports: 28 year old woman with hereditary nonpolyposis colorectal cancer syndrome, colonic adenocarcinoma with microsatellite instability and incidental appendiceal carcinoid tumor without microsatellite instability (Hum Path 2004;35:1564)
Gross: 70% at tip, usually < 1 cm; gray or yellow, well-demarcated, firm, intramural nodules that may narrow or obliterate lumen; proximal tumors may cause obstruction
Micro: may be diffusely within wall or along lumen; usually classic carcinoid insular growth pattern of solid islands of uniform polygonal cells with minimal pleomorphism, retraction of peripheral tumor cells from stroma; tumor cells often within intraappendiceal nerves, angiolymphatic invasion is common; cells have granular eosinophilic cytoplasm with either diffusely scattered or peripherally clumped granules; rarely acinar pattern, clear cell/balloon cell pattern or vacuolated cells; no/rare mitotic activity
Tumors arise in mucosa but bulk is usually within muscularis propria with associated fibrosis and smooth muscle hypertrophy; may penetrate mesoappendix
Tumor cells associated with S100+ Schwann-like cells
Positive stains: chromogranin, neuron specific enolase, serotonin, substance P
Negative stains: CEA, TTF-1, CK7 (usually)
Molecular: may have 18q-, less frequently 11q-; usually diploid by flow cytometry
References: Hum Path 2001;32:1087, Archives 1980;104:272, Hum Path 1990;21:773 (distinction between EC-cell and L-cell types)
Much less common than EC-cell tumors
Minimal metastatic potential
Gross: small nodules at tip, often not identified grossly
Micro: columns, ribbons, acini or small tubules of small round cells with pale eosinophilic cytoplasm and round/oval nuclei with small nucleoli; no/rare mitotic activity; no insular masses
May have dominant glandular pattern resembling metastatic carcinoma
Positive stains: chromogranin B, synaptophysin, CEA, glucagon, peptide YY
Negative stains: mucin, chromogranin A (usually)
Also called mucinous carcinoid, adenocarcinoid, microglandular goblet cell carcinoma
Shows divergent differentiation of normal crypt stem cells (columnar, endocrine, goblet cell, Paneth cell lineages) between typical carcinoma and adenocarcinoma
Less common (6% of all appendiceal carcinoids), usually older patients than classic carcinoid tumors
Up to 20% spread beyond appendix; up to 13% of patients die of tumor (intermediate between classic carcinoid and adenocarcinoma)
5 year survival is 73-84%
Often spreads to ovaries or peritoneal surfaces; metastases may have goblet cell carcinoid, signet ring cell carcinoma or classic carcinoid histology
Poor prognostic factors: solid pattern or carcinomatous pattern in 50%+ of tumor; perineural invasion, lymphatic invasion, spread beyond appendix, serosal involvement at presentation, incomplete excision at appendix base
Treatment: appendectomy, right hemicolectomy if predominant carcinomatous growth pattern, significant mitotic activity or tumor beyond appendiceal wall
Gross: thickened appendiceal wall; usually no gross tumor
Micro: solid tumor cell clusters, crypt-like structures or tubules of mucus-secreting cells distended with mucin resembling goblet cells or signet ring cells, but also with eosinophilic cytoplasm resembling classic carcinoid in some cells; nuclei are bland and monomorphic; may have pools of extracellular mucin; scattered Paneth cells in tumors with crypt like structures; usually spares mucosa and infiltrates muscularis propria and periappendiceal fat; extensive perineural invasion common; 25% of tumor is single cells
Carcinomatous growth pattern: cribriform growth pattern, solid sheets of infiltrating single ring cells; nuclear pleomorphism with frequent mitotic activity (2+ mitotic figures/10 HPF)
Positive stains: mucin (mucicarmine, PAS, PAS diastase, Alcian-blue), CEA, cytokeratin, lysozyme, chromogranin A, serotonin, synaptophysin (usually)
EM: mucinous vacuoles, membrane bound neurosecretory granules
Molecular: loss of heterozygosity of 18q (56%), 16q (38%), 11q (25%), resemble ileal carcinoids more than appendiceal adenocarcinoma (Mod Path 2003;16:1189)
DD: metastatic signet-ring carcinoma (infiltrative, signet-ring cells), classic carcinoid tumor (no goblet cell differentiation, no intracellular mucus vacuoles although may have luminal mucus-lining neoplastic tubules, no Paneth cell differentiation), mucinous adenocarcinomas (more aggressive, irregular fused structures without distinct lumina, often merges with mucosal adenoma)
References: Archives 1979;103:180
Other tumors
Gastrointestinal stromal tumors
Very rare (only 4 cases at AFIP during 1970-1998)
Men 56-72 years
Associated with appendicitis-like symptoms or incidental findings
No deaths due to primary appendiceal GIST, but appendix may also be site of metastases
Gross: partially obliterating nodules expanding appendiceal wall
Micro: spindle cell tumor, often with extracellular collagen globules (skenoid fibers); no atypia, no mitotic activity
Positive stains: CD117, CD34 (often)
Negative stains: alpha smooth muscle actin, S100
DD: neurofibroma, schwannoma (often microtrabecular pattern with surrounding lymphoid cuff, S100+, CD117-, actin-), leiomyosarcoma (actin+, desmin+), inflammatory fibrous polyp
Reference: AJSP 2001;25:1433
Case reports of Burkitt’s lymphoma in children (Hum Path 1980;11:465)
Same system as colon and rectum
Primary tumor (T)
TX: primary tumor cannot be assessed
T0: no evidence of primary tumor
Tis: carcinoma in situ (i.e. intraepithelial or invasion of lamina propria but not through muscularis mucosa into submucosa)
T1: tumor invades submucosa
T2: tumor invades muscularis propria
T3: tumor invades through the muscularis propria into the subserosa, or into non-peritonealized periappendiceal tissues
T4: tumor directly invades other organs or structures or perforates visceral peritoneum
Note: tumor that is adherent to other organs or structures macroscopically is classified as pT4; if no tumor is present in the adhesion, the classification should be pT3
Regional lymph nodes (N)
NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastases
N1: metastasis in 1-3 regional lymph nodes
N2: metastasis in 4 or more regional lymph nodes
Note: a tumor nodule in the periappendiceal adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. If the nodule has an irregular contour, it should be classified in the T category and also coded as microscopic (V1) or macroscopic venous invasion (V2), because there is a strong likelihood that it represents venous invasion
Distant Metastasis (M)
MX: distant metastasis cannot be assessed
M0: no distant metastasis
M1: distant metastasis
Stage grouping Dukes staging Modified Astler-Coller classification
Stage 0: Tis N0 M0 - -
Stage 1: T1-T2 N0 M0 A A, B1
Stage 2A: T3 N0 M0 B B2
Stage 2B: T4 N0 M0 B B3
Stage 3A: T1-T2 N1 M0 C C1
Stage 3B: T3-T4 N1 M0 C C2/C3
Stage 3C: Any T N2 M0 C C1/C2/C3
Stage 4: Any T, any N, M1 - D
Describe length and greatest diameter, external surface (fibrinous exudate, perforation), luminal patency, mucosa, details of any unusual lesions
Submit longitudinal or cross section of distal tip (common site of carcinoid tumors), cross sections from middle and margin of resection
Features to report for tumors
Tumor size
Histologic type
Histologic grade
Depth of invasion
Angiolymphatic invasion
Perineural invasion
Margin involvement (surgical, radial)
Lymph node involvement (total involved, total examined)
Note: as of 1Apr2005, there is no specific CAP protocol for appendiceal tumors
End of Appendix outline/chapter